The objective of this proposal is to elucidate the mechanism by which cholera enterotoxin (CT) and E. coli enterotoxin (ECT) stimulate adenosine 3'-5' cyclic monophosphate (cAMP) formation and steroidogenesis in cultured adrenal tumor cells. The heat-labile enterotoxin from culture filtrates of E. coli strain Hl0407 will be concentrated and purified through a membrane ultrafiltration system and column chromatography. Next, the physical and chemical properties of purified ECT will be studied and compared to CT. Then, the effects of enterotoxins on cAMP formation and steroidogenesis in adrenal tumor cells in tissue culture will be compared to ACTH. Inhibitors, including brain ganglioside, choleragenoid, and specific antisera will be utilized to determine if both enterotoxins compete for the same adrenal membrane receptor site. The effects of membrane active drugs and adenyl cyclase inhibitors on enterotoxin induced cAMP formation will be studied to determine the nature of the membrane receptor site and the basis for the lag period prior to steroidogenesis. This study should develop agents which inhibit enterotoxin activity in cultured adrenal cells and may be clinically important. A pilot screening program will determine the role toxigenic E. coli play in causing acute infantile diarrhea.